This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. These studies focus on physiologically transient transmembrane complexes that are required for disease progression and novel therapies to treat infections. These two research areas each encompass three sub-projects. Our first focus is on transmembrane complexes. Seemingly disparate signaling proteins form complexes across the membrane, but likely share over-arching mechanisms of signaling mediated by conformational changes, electrostat-ics, or changes in dynamics. Our studies use several model systems. Determination of the structures of transmembrane signaling complexes is at the cutting edge of structural biology. The initial crystals diffract poorly and require diffraction-based feedback to improve the diffraction limit to reasonable resolution. Our second focus is on developing novel therapies for bacterial and HIV infections. Here, we are determining the structures of enzymes that synthesize therapeutic compounds in order to improve or tune the efficiency of the chemical reaction.